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Perspectives on development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

ABSTRACT: The recent outbreak of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been characterized by the World Health Organization (WHO) as a controllable global pandemic. The spike (S) glycoprotein mediates binding to the angiotensin-converting enzyme 2 (ACE2) receptor for virus entry and also services as the target of virus-neutralizing antibodies, making it an attractive and leading viral antigen for vaccine development. No vaccine against any human coronavirus is available to date. In learning from the experience of developing Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV vaccine candidates in preclinical and clinical trials, the most promising strategies for SARS-CoV-2 vaccines should employ viral-vector platforms, properly adjuvanted recombinant protein or DNA/mRNA encoding an engineered sequence of trimeric S protein in pre-fusion conformation.

SUBMITTER: Zhang C

PROVIDER: S-EPMC7644209 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Perspectives on development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Zhang Chao C Zhou Chenliang C Shi Li L Liu Ge G

Human vaccines & immunotherapeutics 20200922 10

The recent outbreak of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been characterized by the World Health Organization (WHO) as a controllable global pandemic. The spike (S) glycoprotein mediates binding to the angiotensin-converting enzyme 2 (ACE2) receptor for virus entry and also services as the target of virus-neutralizing antibodies, making it an attractive and leading viral antigen for vaccine development. No vacc ...[more]

PMID: 32961082

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Project description:BackgroundThe world has been suffering from the COVID-19 pandemic (officially declared by WHO in March 2020), caused by the severe acute respiratory β-coronavirus 2 (SARS-CoV-2) since the last week of December 2019. The disease was initially designated as a Public Health Emergency of International Concern on January 30, 2020. In order to protect the health of mass public, an array of research on drugs and vaccines against SARS-CoV-2 has been conducted globally. However, the emerging variants of SARS-CoV-2, i.e., Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) variants which evolved in late 2020 and the Omicron variant (B.1.1.529) which emerged in November 2021 along with its subvariant BA.2 which was first identified in India and South Africa in late December 2021, have raised the doubt about the efficiency of the currently used vaccines especially in terms of the consistent potential to produce neutralizing antibodies targeting the viral spike (S) protein.Main body of the abstractThe present review discussed the functional details of major vaccines regarding their efficiency against such variants during the pandemic. Overall, the mRNA vaccines have shown around 94% effectiveness; the adenovector vaccine showed approximately 70% efficacy, whereas Sputnik V vaccines showed around 92% effectiveness; the inactivated whole-virus vaccine CoronaVac/PiCoVacc and BBIBP-CorV showed a varying effectiveness of 65-86% according to the geographic locations; the subunit vaccine NVX-CoV2373 has shown 60-89% effectiveness along with the global regions against the wild-type SARS-CoV-2 strain. However, reduced effectiveness of these vaccines against the SARS-CoV-2 variants was noticed which is suggestive for the further administration of booster dose.Short conclusionMaximum variants of SARS-CoV-2 emerged during the second wave of COVID-19; and extensive studies on the viral genomic sequences from all geographical locations around the world have been conducted by an array of groups to assess the possible occurrence of mutations(s) specially within the receptor binding domain of the viral spike (S) protein. Mutational similarities and the new or critical mutations within all variants have been clearly identified so far. The study of effectiveness of the currently used vaccines is also ongoing. The persistence of memory B cell action and the other immune components as well as the administration of booster dose is expected to mitigate the disease.

Project description:BackgroundThe spread of a novel coronavirus termed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in China and other countries is of great concern worldwide with no effective vaccine. This study aimed to design a novel vaccine construct against SARS-CoV-2 from the spike S protein and orf1ab polyprotein using immunoinformatics tools. The vaccine was designed from conserved epitopes interacted against B and T lymphocytes by the combination of highly immunogenic epitopes with suitable adjuvant and linkers.ResultsThe proposed vaccine composed of 526 amino acids and was shown to be antigenic in Vaxigen server (0.6194) and nonallergenic in Allertop server. The physiochemical properties of the vaccine showed isoelectric point of 10.19. The instability index (II) was 31.25 classifying the vaccine as stable. Aliphatic index was 84.39 and the grand average of hydropathicity (GRAVY) was - 0.049 classifying the vaccine as hydrophilic. Vaccine tertiary structure was predicted, refined and validated to assess the stability of the vaccine via Ramachandran plot and ProSA-web servers. Moreover, solubility of the vaccine construct was greater than the average solubility provided by protein sol and SOLpro servers indicating the solubility of the vaccine construct. Disulfide engineering was performed to reduce the high mobile regions in the vaccine to enhance stability. Docking of the vaccine construct with TLR4 demonstrated efficient binding energy with attractive binding energy of - 338.68 kcal/mol and - 346.89 kcal/mol for TLR4 chain A and chain B respectively. Immune simulation significantly provided high levels of immunoglobulins, T-helper cells, T-cytotoxic cells and INF-γ. Upon cloning, the vaccine protein was reverse transcribed into DNA sequence and cloned into pET28a(+) vector to ensure translational potency and microbial expression.ConclusionA unique vaccine construct from spike S protein and orf1ab polyprotein against B and T lymphocytes was generated with potential protection against the pandemic. The present study might assist in developing a suitable therapeutics protocol to combat SARSCoV-2 infection.

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Perspectives on development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

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Perspectives on development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

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